Polymorphisms of ATP-binding cassette, sub-family A, member 4 (rs560426 and rs481931) and non-syndromic cleft lip/palate: A systematic review and meta-analysis

Abstract

Background A number of gene loci are closely associated with the incidence of non-syndromic cleft lip/palate (NSCL/P). Herein, this meta-analysis assessed the association between ATP-binding cassette, sub-family A, member 4 (ABCA4) polymorphisms (rs560426 and rs481931) and the risk of NSCL/P by reviewing case-control studies.Methods Four databases including Scopus, Cochrane Library, Web of Science, and PubMed were searched for articles published up to December 2018. The Review Manager 5.3 software was used to calculate the crude odds ratio (OR) and 95% confidence interval (CI).Results Of 82 retrieved studies, 12 were analyzed in this meta-analysis (2,859 NSCL/P patients and 3,792 controls for ABCA4 rs560426 polymorphism and 1,333 NSCL/P patients and 1,884 controls for ABCA4 rs481931 polymorphism). There was no significant association between the polymorphisms and the risk of NSCL/P, with the exception of the allelic model (OR=1.13; 95% CI: 1.01, 1.27; p=0.03), the homozygote model (OR=1.53; 95% CI: 1.01, 2.31; p=0.04), and the recessive model (OR=1.30; 95% CI: 1.03, 1.63; p=0.03) in the Asian ethnicity for rs560426 polymorphism.Conclusion The findings confirmed that G allele and GG genotype of rs560426 polymorphism were significantly associated with the risk of NSCL/P in the Asian population, but not for rs481931polymorphism. Also, there was no association between both polymorphisms (rs560426 and rs481931) with the risk of NSCL/P in the Caucasian and the mixed ethnicities, as well as the source of controls. Therefore, ethnicity may play a significant role in this association.